Thrombomodulin-modified Thrombin Generation Assay (TGA-TM) in Patients With Critical Infections

NCT04356144 | Completed

• 1 other identifier: TGA-TM-Critical-2019
• Study Type: observational
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

Inflammation and abnormalities in laboratory coagulation tests are inseparably tied. For example, coagulation abnormalities are nearly universal in septic patients. Coagulation disorders have also been reported in many patients with severe courses of Coronavirus disease 2019 (Covid-19). But it is difficult to assess these changes. Global coagulation tests have been shown to incorrectly assess in vivo coagulation in patients admitted to intensive care units. But other tests are available. Thrombin generation assay (TGA) is a laboratory test which allows the assessment of an individual's potential to generate thrombin. But also in conventional TGA the protein C system is hardly activated because of the absence of endothelial cells (containing natural thrombomodulin) in the plasma sample. Therefore the investigators add recombinant human thrombomodulin to a conventional TGA. Thereby the investigators hope to be able to depict in vivo coagulation more closely than global coagulation tests do.

Conditions

Disseminated Intravascular Coagulation; Critical Illness; Sars-CoV2; Viral Infection; Coagulation Disorder, Blood; Covid19

Keywords

TGA; thrombin generation; Sars-CoV2; ROTEM; rotational thromboelastometry; viscoelastic assay; thrombomodulin

Outcome Measures

Primary Outcomes (4)

• ETP (AUC) without rhThrombomodulin (rhTM)

  nM;

  6 months

• ETP (AUC) with rhThrombomodulin (rhTM)

  nM;

  6 months

• ETP-ratio

  Ratio of endogenous thrombin potential (ETP) with rhTM to ETP without rhTM

  6 months

• ETP-Normalisation

  Comparison of ETP-ratios from ICU patients and ETP-ratios from citrated plasma samples from healthy donors

  6 months

Study Arms (1)

Critical infection

Patients with signs of infection with SARS-CoV-2 or already diagnosed infection with SARS-CoV-2 admitted to the ICU

Diagnostic Test: Thrombin Generation Assay (TGA); Diagnostic Test: Thrombomodulin Modified Thrombin Generation Assay (TGA-TM)

Interventions

Thrombin Generation Assay (TGA) DIAGNOSTIC_TEST

TGA via a fluorimetric module. Coagulation cascade is activated upon addition of different concentrations of tissue factor and phospholipids. The fluorogenic substrate Z-Gly-Gly-Arg-AMC (ZGGR-AMC) is cleaved by formed thrombin over time. By plotting the changes in fluorescence as a function of time (cnt/min), it depicts the "Thrombin Generation Curve" (thrombin generated - plotted against time). The area under the thrombin curve is defined as the endogenous thrombin potential (ETP).

Critical infection

Thrombomodulin Modified Thrombin Generation Assay (TGA-TM) DIAGNOSTIC_TEST

Recombinant Human Thrombomodulin (TM) is added to the conventional TGA. When recombinant TM is added, the protein C system is fully activated and therefore the ETP obtained reflects both the anti- and procoagulant factors.

Critical infection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

60 critically ill patients with signs of infection with SARS-CoV2 or proven infection with SARS-CoV-2 admitted to Intensive Care Units (ICU).

You may qualify if:

• Admission to ICU
• Clinical signs of infection with SARS-CoV-2 or already diagnosed infection with SARS-CoV-2
• Neutrophil-Lymphocyte Ratio (NLR) \>3

You may not qualify if:

• Intake of oral anticoagulants or any kind of parenteral therapeutic anticoagulation prior to ICU admission
• Congenital coagulation disorder
• Treatment with Prothrombin complex concentrate (F. II, VII, IX, X) or activated Prothrombin complex within past 48 hours
• Treatment with recombinant factor VIIa (e.g. eptacog alfa) within past 48 hours
• Treatment with recombinant protein C within past 48 hours
• Active bleeding
• Acute myocardial infarction
• HIV infection
• Chronic pancreatitis
• Liver cirrhosis

Sponsors & Collaborators

• Medical University of Vienna: lead
• Medical Scientific Fund of the Mayor of Vienna: collaborator

Study Sites (1)

Medical University Vienna

Vienna, 1090, Austria

Location

MeSH Terms

Conditions

Disseminated Intravascular Coagulation; Critical Illness; Virus Diseases; Blood Coagulation Disorders; COVID-19

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Thrombophilia; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 15, 2020
• First Posted: April 22, 2020
• Study Start: April 15, 2020
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: March 23, 2021

Record last verified: 2021-03

Locations

AU (1)